The overall objectives of this research program are to understand partitioning of energy input (VO2) amongst the major energy consuming processes and the relation between energy input and mechanical output in the whole (isolated) rabbit heart under normal conditions and during hypertrophy. We have recently detected increases in both contractile efficiency and economy in rabbit hearts subjected to minimal pressure overload. These alterations in mechanenergetic parameters cannot be explained by changes in isomyosin composition. This proposal is designed to delineate the time course and magnitude of changes in mechanoenergetic parameters during the progression of pressure overload produced by cellophane wrap of the kidneys. In addition, by accurate partitioning of energy input into components related to crossbridge cycling, excitation- contraction coupling and recovery metabolism and coupling these observations to measurements of isomyosin composition and myofibrillar ATPase activity, we will begin to delineate the mechanism of these alterations in mechanoenergetics. The preparation we employ for our acute studies is a red cell-perfused, isolated rabbit heart preparation. The hearts will be studied at various times after the onset of pressure overload. These hearts will be compared to both normal controls and hearts from animals with hypothyroidism, since both pressure overload and hypothyroid hearts have identical isomyosin composition. Parallel studies in isolated muscle strips will be employed to determine if alterations in recovery metabolism are responsible for mechanoenergetic alterations during pressure overload. We predict that the evidence gathered will support an early change in the contractile proteins, unrelated to isomyosin composition, as the mechanism of increased contractile efficiency and economy. It is possible that alterations in excitation-contraction coupling may further contribute at later phases of pressure overload. The experiments proposed should provide a foundation for subsequent understanding of the cellular/molecular mechanism of altered contractile proteins in pressure overload.